77 articles - From Friday Aug 05 2022 to Friday Aug 12 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
ESO-ESMO 5th International Consensus Guidelines for Breast Cancer in Young Women (BCY5). Areas of research priorities, as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA). |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin. This ARIES trial confirmed the activity and safety of avelumab for treating mUC, adding a new therapy option to the armamentarium of checkpoint inhibitors already approved for platinum-ineligible, locally advanced/mUC. |
| Blood |
Clonal germinal center B cells function as a niche for T-cell lymphoma. The genes expressed in aberrantly expanded GCB cells in murine tumors were also broadly expressed in the B-lineage cells of TET2-mutant human AITL. Therefore, ACH-derived GCB cells could undergo independent clonal evolution and support the tumorigenesis in AITL via the CD40-CD40LG axis. |
Combined Immunosuppression for Acquired Hemophilia A: CyDRi is a Highly Effective Low Toxicity Regimen. In conclusion, the CyDRi regimen produced markedly higher complete remission rates and overall survival than currently used sequential regimens. Taken together, CyDRi proved to be an attractive option for the immunosuppression of elderly AHA patients. |
Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCL) also expressed lower levels of CD48 than normal T-cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK cell surveillance. Thus, this study demonstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK cell mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK cell-associated immunotherapies. |
Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism. These findings should be a call to action to increase awareness and provide evidence-based strategies for preventing and treating AUB in this setting. This was an academic study (NCT04748393 at no funding was received. |
Long Term Outcomes in Patients with Relapsed or Refractory Hairy Cell Leukemia Treated with Vemurafenib Monotherapy. S. clinical trial (NCT01711632) including the ORR, relapse free survival, clinical factors associated with improved survival as well as outcomes after retreatment with vemurafenib or alternative agents. |
MAPK-interacting kinase 1 (Mnk1) regulates platelet production, activation, and thrombosis. In vivo, Mnk1 ablation in platelets protected against thromboembolism. These results provide previously unrecognized evidence that Mnk1 regulates mRNA translation and cellular activation in platelets and megakaryocytes, endomitosis and thrombopoiesis, and thrombosis. |
MINIMAL RESIDUAL DISEASE-DRIVEN TREATMENT INTENSIFICATION WITH SEQUENTIAL ADDITION OF IBRUTINIB TO VENETOCLAX IN R/R CLL. This sequential MRD-guided approach led to uMRD4 in 33/38 patients (87%) with venetoclax monotherapy or combined with ibrutinib., delivering treatment combination only in a fraction, and ultimately identifying the few patients benefiting from continuous therapy. Clinical trial number: NCT04754035. |
Single-cell analysis of acute lymphoblastic and lineage ambiguous leukemia - approaches and molecular insights. In addition, we discuss the importance of dynamic interactions occurring between leukemia cells and the non-leukemia microenvironment. We discuss potential opportunities and limitations of single-cell sequencing for the study of ALL biology and treatment responsiveness. |
Single cell genomics in AML: extending the frontiers of AML research. In recent years, the field of single cell genomics has led to unprecedented strides in the ability to characterize cellular heterogeneity and holds promise for the study of AML. In this review, we will highlight advancements in single cell technologies, outline important shortcomings in our understanding of AML biology and clinical management, and discuss how single cell genomics can not only address these shortcomings, but also provide unique opportunities in basic and translational AML research. |
| Blood Adv |
Early cytopenias and infections after standard of care idecabtagene vicleucel On univariate analysis, high pre-CAR-T marrow myeloma burden (>/= 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade =3 anemia at pre-LD were associated with grade =3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection. |
EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress. Treatment of hyaluronan-injected mice with anti-CD44 antibody or |
Higher doses of tisagenlecleucel associate with improved outcomes: a report from the pediatric real-world CAR consortium. Moreover, higher doses of tisagenlecleucel were not associated with increased toxicity. As the current tisagenlecleucel package insert dose-range remains broad, this work has implications in regard to targeting higher cell doses to optimize patients for long-standing remission. |
Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations. PHATE affinity-based transition analysis identified putative precancerous circulating populations characterized by an intermediate stage of gene expression and mutation level between the normal CD4+ T-cells and malignant CTCL cells. We further revealed the therapeutic potential of targeting CD82 and JAK that endow the malignant CTCL cells with survival and proliferation advantages. |
Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials. |
MOZ is critical for the development of MOZ/MLL-fusion-induced leukemia through regulation of Hoxa9/Meis1 expression. MOZ-TIF2 and endogenous Moz binding and active histone modifications were also severely reduced at the Meis1 locus in Moz-deficient MOZ-TIF2 and MLL-AF9 AML cells. These results suggest that endogenous MOZ is critical for MOZ/MLL-fusion-induced AML development and maintains fusion binding and active chromatin signatures at target gene loci. |
Real-world effectiveness of caplacizumab vs standard of care in immune thrombotic thrombocytopenic purpura. In summary, caplacizumab reduced exacerbations and refractoriness compared to standard of care regimens. When administered within the first 3 days after PEX it also provided a faster clinical response, reducing hospitalization time and the need for PEX. |
Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia. In path analysis, indirect relationships between blood oxygenation and cognition, mediated by network properties, were better supported than direct alternatives, with an indirect relationship between low SpO2 and PSI in patients, mediated by structural connectivity efficiency in a subnetwork of the brain differing from controls. Our findings are consistent with the notion that cognitive impairment is primarily mediated by hypoxic-ischemic effects on normal-appearing white matter, and highlight the utility of network-based methods in providing biomarkers of cognitive dysfunction in SCA patients. |
Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. The data demonstrate that minor and major surgeries can be performed safely in PwHA receiving emicizumab prophylaxis. These trials are registered at as NCT02622321, NCT02795767; NCT02847637, and NCT03020160. |
Targets of autoantibodies in acquired hemophilia A are not restricted to factor VIII: data from the GTH-AH 01/2010 study. These antibodies did not stain HEp-2 cells used for ANA detection. In conclusion, a diverse pattern of autoantibodies is associated with AHA, suggesting that a more general breakdown of immune tolerance might be involved in its pathology. |
The Impact of Race, Ethnicity, and Obesity on CAR T-cell Therapy Outcomes. However, toxicity profiles may vary. Therefore, efforts to improve access to CAR therapy for underrepresented populations and elucidate mechanisms of differential toxicity among demographic groups should be prioritized. |
| Haematologica |
ARID5B influences B cell development and function in mouse. In addition, increased mitochondrial oxygen consumption rate of naïve or stimulated B cells of Arid5bOE mice was observed, compared to wildtype counterparts. Taken together, our results indicate that ARID5B may play important role in B-cell development and function. |
Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia. In the 230 patients evaluated at diagnosis and intensively treated, high ABC activity was a predictive factor for primary resistance, and in multivariate analysis including full molecular data, an independent factor for event-freesurvival (p=0.0370). JC-1 +/- CsA assay could be used at diagnosis to predict AML ontogeny and to complete prognosis evaluation in addition to new molecular markers. |
Early expression of CD94 and loss of CD96 on CD8+ T cells after allogeneic SCT is predictive of subsequent relapse and survival. Furthermore, reduced expression of the activatory molecule CD96 was associated with 2.2 fold increased risk of relapse and 1.9 fold reduction in survival. This work identifies CD94 and CD96 as potential targets for CD8-directed immunotherapy in the very early phase following allogeneic transplantation with the potential to reduce long term relapse rates and improve patient survival. |
Molecular monitoring of T-cell kinetics and migration in severe neurotoxicity after real-world CD19-specific chimeric antigen receptor-T cell therapy. Interestingly, a major fraction of eventually dominating hyperexpanded T-cell clones were of non-CAR-T cell derivation. These findings hint to a role of therapy-refractory T-cell clones in severe ICANS development and prompt future systematic research to determine if CAR-T cells may serve as 'door openers' and to further characterize both CARpositive and non-CAR-T cells to interrogate the transcriptional signature of these possibly pathologic T cells. |
Osteoprogenitor SFRP1 prevents exhaustion of hematopoietic stem cells via PP2A-PR72/130-mediated regulation of p300. Our findings show that osteoprogenitor Sfrp1 is essential for maintaining HSC function. Furthermore, pharmacological downregulation of nuclear Catenin beta-1/phospho-p300 association is a new strategy to restore poor HSC function. |
Potent preclinical activity of FLT3-directed chimeric antigen receptor T cell immunotherapy against FLT3-mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia. We further demonstrate significant in vitro and in vivo activity of bispecific CD19xFLT3CART against KMT2A-rearranged ALL and posit that this additional approach might also diminish potential antigen escape in these high-risk leukemias. Our preclinical data credential FLT3CART as a highly effective immunotherapeutic strategy for both FLT3-mutant AML and KMT2A-R ALL that is poised for further investigation and clinical translation. |
Relative impact of residual cytogenetic abnormalities and flow cytometric measurable residual disease on outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia. To examine how residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry (MFC) may refine risk assessment before HCT, we analyzed 506 adults with cytogenetically abnormal AML who underwent both routine karyotyping and MFC MRD testing before receiving a first allograft while in morphologic remission. Testing for residual cytogenetic abnormalities and MFC MRD identified four groups of patients with differential relapse-free survival (RFS, hazard ratio [HR]=1.63 for Cytoabnormal/MFCnegative [P=0.01, n=63], HR=3.24 for Cytonormal/MFCpositive [P. |
Translational readthrough at F8 nonsense variants in factor VIII B domain contributes to residual expression and lowers inhibitor association. These original findings into HA molecular genetics, and particularly into genotype-phenotype relationships related with disease treatment, demonstrate that B-domain features favour PTC readthrough output. This provides a potential molecular mechanism contributing to differential PTC-associated inhibitor occurrence, with translational implications for a novel, experimentally based classification of F8 nonsense variants. |
| Leukemia |
A phase two study of high dose blinatumomab in Richter's syndrome. The patient who achieved CR had the lowest levels of immune checkpoint expression. Simultaneous targeting with immune checkpoint blockade, especially PD1 inhibition, which has already demonstrated single-agent efficacy in RS, could achieve synergistic killing and enhance outcomes. |
Alternatively spliced CSF3R isoforms in SRSF2 P95H mutated myeloid neoplasms. CD34+ |
An immunity and pyroptosis gene-pair signature predicts overall survival in acute myeloid leukemia. Our web-tool implementation of the IPRP score and a simple 4-factor nomogram enables practical and robust risk scoring for AML patients. Even though developed for AML patients, our pan-cancer analyses demonstrate a wider application of the IPRP signature for prognostic prediction and analysis of tumor-immune interplay also in multiple solid tumors. |
Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial. When evaluating two-fold variable combinations the most striking effects were found for WT1:NPM1 (with NPM1 mutation abrogating the negative effect of WT1 mutation), and for WT1:treatment (with midostaurin exerting a beneficial effect in WT1-mutated AML). This targeted gene sequencing study provides important, novel insights into the genomic background of FLT3-mutated AML including the prognostic impact of co-mutations, specific gene-gene interactions, and possible treatment effects of midostaurin. |
Minimal residual disease in BCR::ABL1-positive acute lymphoblastic leukemia: different significance in typical ALL and in CML-like disease. Early distinguishing typical BCR::ABL1-positive ALL and CML-like patients is essential to enable optimal treatment approach in upcoming protocols. For the typical ALL, tyrosine-kinase inhibitors and concurrent chemotherapy with risk-directed intensity should be recommended; in the CML-like disease, no relevant prognostic feature applicable for therapy tailoring was found so far. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
| Ann Oncol |
Cancer: Slaying the 9-headed Hydra. Importantly, molecular interrogation has revealed that metastatic cancers are distinct from each other and complex. Therefore, it is conceivable that rational personalized drug combinations will be needed to eradicate cancers, and eradication will be necessary to mitigate clonal evolution and resistance. |
| Blood |
| J Hematol Oncol |
Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity. In this review, we discuss the common and distinct metabolic profiles of Tregs in peripheral tissues and the TME, as well as the differences between Tregs and other conventional T cells in their metabolic preferences. By focusing on the critical roles of different metabolic programs, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, fatty acid synthesis, and amino acid metabolism, as well as their essential regulators in modulating Treg proliferation, migration, and function, we hope to provide new insights into Treg cell-targeted antitumor immunotherapies. |
| Leukemia |
Letters to the editors and authors’ replies
| Ann Oncol |
| Blood Cancer J |
| J Hematol Oncol |
Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents. Overall, the most frequently reported treatment-related adverse events were nausea (45%), diarrhea (35%), decreased appetite (35%), fatigue and neutropenia (both 30%). Single-agent oral eltanexor was active, safe, and well tolerated in patients with higher-risk, primary HMA-refractory MDS. |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Leukemia |